Sandbox Reserved 1502: Difference between revisions
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HIV integrase is an enzyme required for the integration of viral DNA into the host genome. The process of integration can be divided into two sequential reactions. In the first one, named 3'-processing, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides. The second step is the insertion of the processed 3′-viral DNA ends into the host chromosomal DNA by a trans-esterification reaction. This is the strand transfer. | HIV integrase is an enzyme required for the integration of viral DNA into the host genome. The process of integration can be divided into two sequential reactions. In the first one, named 3'-processing, the enzyme removes di- or trinucleotides from viral DNA ends to expose 3′-hydroxyls attached to the invariant CA dinucleotides. The second step is the insertion of the processed 3′-viral DNA ends into the host chromosomal DNA by a trans-esterification reaction. This is the strand transfer. | ||
== Reserach on antiviral == | |||
Research on HIV show that the integrase use a protein, the LEDGF/p75 cofactor, so as to the preintegration complex is ligated to the DNA. | |||
Some recents experimental antiviral inhibe this interaction and unable the integrase to interact with the cofactor. Thus, the DNA wouldn’t be inserted into the genome of the cell. | |||
== Structure == | == Structure == | ||
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HIV-1 integrase is composed of three domains: the N-terminal (residues 1-49), the core domain (residues 50-212) and the C-terminal domain (residues 213-288). The core domain is responsible for the catalytic activity of the enzyme. It contains three acidic residues, the D,D-35-E motif which plays a key role in catalysis. The N-terminal domain includes the conserved HHCC motif, which binds zinc. The C-terminal domain is less well conserved. [http://www.jbc.org/content/276/26/23213/F2.expansion.html] | HIV-1 integrase is composed of three domains: the N-terminal (residues 1-49), the core domain (residues 50-212) and the C-terminal domain (residues 213-288). The core domain is responsible for the catalytic activity of the enzyme. It contains three acidic residues, the D,D-35-E motif which plays a key role in catalysis. The N-terminal domain includes the conserved HHCC motif, which binds zinc. The C-terminal domain is less well conserved. [http://www.jbc.org/content/276/26/23213/F2.expansion.html] | ||
====Structure and role of the core domain in the integration==== | |||
[[Image:Domain_HIV_Integrase.jpg]] | [[Image:Domain_HIV_Integrase.jpg]] | ||
[[Image:HIV Integrase sequence.jpg]] | [[Image:HIV Integrase sequence.jpg]] | ||